Decreased protein synthesis of transforming lymphocytes from aged humans: relationship to impaired mitogenesis with...

Recent studies have indicated that the decline in mitogenesis during the aging process may be related to intracellular defects that become apparent when the cells are subjected to the metabolic stress of cell transformation. We provide the first report of an age-related decline in protein synthesis in human lymphocytes exposed to phytohemagglutinin. This impairment in protein synthetic capacity from aged subjects' transforming cells is apparent from 24 to 72 h of culture. By 72 h of culture the incorporation of radiolabeled leucine in stimulated cells from elderly subjects is about half that for the young. However, cells from the aged have an increased protein content in the face of decreased synthesis suggesting a degradation defect. Since protein synthesis may be necessary for the induction of key effectors which activate glycolysis (which is necessary for transformation), we sought to relate the impaired protein synthesis to the impaired glycolytic enzyme induction with age. Cycloheximide totally inhibited glycolytic enzyme induction as well as cell transformation. A defect in protein synthesis with age may interfere with new enzyme synthesis which is necessary to activate requisite pathways for mitogenesis such as glycolysis.